A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.
Laczkó Dorottya, Hogan Michael J, Toulmin Sushila A, Hicks Philip, Lederer Katlyn, Gaudette Brian T, Castaño Diana, Amanat Fatima, Muramatsu Hiromi, Oguin Thomas H, Ojha Amrita, Zhang Lizhou, Mu Zekun, Parks Robert, Manzoni Tomaz B, Roper Brianne, Strohmeier Shirin, Tombácz István, Arwood Leslee, Nachbagauer Raffael, Karikó Katalin, Greenhouse Jack, Pessaint Laurent, Porto Maciel, Putman-Taylor Tammy, Strasbaugh Amanda, Campbell Tracey-Ann, Lin Paulo J C, Tam Ying K, Sempowski Gregory D, Farzan Michael, Choe Hyeryun, Saunders Kevin O, Haynes Barton F, Andersen Hanne, Eisenlohr Laurence C, Weissman Drew, Krammer Florian, Bates Paul, Allman David, Locci Michela, Pardi Norbert
Immunity · 2020 · PMID 32783919 · 인용 393
SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice.
We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.